Thiele J, Wickenhauser C, Kvasnicka H M, Varus E, Schneider C, Müller H, Beelen D W
Institute of Pathology, University of Cologne, Germany.
Acta Haematol. 2003;109(4):176-83. doi: 10.1159/000070966.
Until now, studies on mixed chimerism (MCh) after allogeneic bone marrow transplantation (BMT) have predominantly focused on the B- and T-lymphocyte population, but not on distinct myeloid cell lineages like nucleated erythroid precursors and megakaryocytes. To evaluate the lineage-restricted MCh more explicitly in 10 patients with chronic myelogenous leukemia (CML), a quantitative analysis was performed on bone marrow biopsies following a sex-mismatched host/donor constellation. Techniques included immunophenotyping (antiglycophorin C, CD61) for the identification of erythro- and megakaryopoiesis and a simultaneously conducted genotyping with x- and y-chromosome-specific DNA probes. Normal bone marrow and specimens taken before BMT served as controls. Contrasting a total gender-dependent sex-typing in the latter samples in the early and late posttransplant period (up to 586 days), 3-9% erythroid precursors and about 16% megakaryocytes revealed a host-type origin. This significantly higher number of host megakaryocytes is explained by their polyploidy generating an increased probability to detect positive signals at a certain section level of the corresponding biopsies. A striking conversion of MCh to a recipient cell type was found in leukemic relapse with a more than 90% host-derived erythroid and megakaryocytic cell population in 4 patients approximately 643 days after BMT.
到目前为止,关于异基因骨髓移植(BMT)后混合嵌合体(MCh)的研究主要集中在B淋巴细胞和T淋巴细胞群体上,而没有关注有核红细胞前体和巨核细胞等不同的髓系细胞谱系。为了更明确地评估10例慢性粒细胞白血病(CML)患者的谱系限制性MCh,在性别不匹配的宿主/供体组合后,对骨髓活检进行了定量分析。技术包括用于鉴定红细胞生成和巨核细胞生成的免疫表型分析(抗血型糖蛋白C、CD61)以及同时使用X和Y染色体特异性DNA探针进行基因分型。正常骨髓和BMT前采集的标本用作对照。在移植后早期和晚期(长达586天),对比后一组样本中完全依赖性别的性别分型,3-9%的红细胞前体和约16%的巨核细胞显示为宿主型起源。宿主巨核细胞数量明显更多,这是因为它们的多倍体性增加了在相应活检的特定切片水平检测到阳性信号的概率。在白血病复发时发现MCh显著转变为受体细胞类型,在4例患者中,BMT后约643天,超过90%的红细胞和巨核细胞群体来源于宿主。